Professor Koh Seong-ho of the Department of Neurology is a doctor and a researcher who is interested in treating the aftereffects of Alzheimer's disease and cerebral infarction. He received his doctorate degree from Hanyang University and used to work at Harvard University as a research fellow. Koh is general affairs manager of the Korean Dementia Association, and associate managing editor of the Journal of Clinical Neurology. His recent paper, “Neuroprotective Effects of Acetyl-L-Carnitine Against Oxygen-Glucose Deprivation-Induced Neural Stem Cell Death”, focuses on acetyl-L-carnitine’s function of protecting and enhancing the regeneration of neural stem cells.

Koh explains the neuroprotective function of acetyl-L-carnitine.

Acetyl-L-carnitine, or ALCAR for short, is a source of energy. It is an ingredient for mitochondria inside stem cells as well as other cells. When cerebral infarction occurs, which is when arteries in the brain get clogged, oxygen and glucose become deprived as blood circulation is blocked. In this situation, when oxygen glucose deprivation (OGD) occurs, mitochondria receive damage as well. The coenzyme inside the mitochondria, which makes energy for the stem cells, is pushed out, resulting in cell death. There are three well-known types of cell death, which are necrosis, apoptosis, and autophagy. Koh’s research is focused on apoptosis where cell death occurs gradually, unlike necrosis. ALCAR can assist apoptosis in preserving and reviving the cells.

Koh conducted an experiment using neural stem cells extracted from rats, and exposed the cells to an OGD environment similar to cerebral infarction. By increasing the concentration levels of ALCAR to that of stem cells that died of OGD, Koh found that they could be revived owing to ALCAR. “What we found out from our study is that ALCAR is not only a supporting material for mitochondria’s metabolism, but it also protects and regenerates stem cells,” Koh said.

Neural stem cells of rats. Nestin, Ki67, and DAPI are markers that show that these are neural stem cells. (Photo coutesy of Koh)

“When a cell dies, free oxygen radicals are created. Free oxygen radicals can be emerged as a response to stress caused by diseases. Too much free oxygen radicals may stop proteins from functioning, induce inflammation, cause even more cell death and increase pathogens,“ described Koh. ALCAR can help reserve some cells to proliferate when cell death occurs. This can be done by passing on energy, and reducing free oxygen radicals and oxidative stress caused by the radicals. “Through the research, we found out that in an OGD environment where the survival rate of the cell was only 40%, the cells regenerated up to 80% with ALCAR- twice as much,” Koh explained.

The bar graph shows the cell survival rate and the line graph shows the cell death rate. The black bar shows an OGD state where ALCAR does not exist. From this graph, we can clearly see that ALCAR revives the dead cells. (Photo courtesy of Koh)

The distinct contrast between cell population (purple dots) and the second and third petri dishes shows ALCAR'S capacity for regenerating cells. The graph below it shows the population of cells before and after ALCAR exposure. (Photos courtesy of Koh)

“What we discovered is ALCAR’s function of manipulating survival-related proteins and death-related proteins, which reduces apoptosis,” Koh reiterated. Cells are immensely complicated systems, and one of those receive various signals sent by proteins with regard to their types and locations in the human body. The study concentrated on the signals that PI3K (phosphoinositide 3-kinase) send which are significant to the survival, proliferation, and differentiation of cells. ALCAR activates PI3K, thereby controlling the survival and death of related proteins. “We examined protein levels and then used a blocker that obstruct the signal path of PI3K. We could see that the effects of ALCAR was impeded as well due to the blockage, proving that ALCAR is associated with PI3K and its pathway,” Koh elaborated.

"Bad results could turn out to be a trigger for another good research."

According to Koh, there isn't much treatment for the aftereffects of brain-related diseases such as cerebral infarction and Alzheimer’s disease, even though a lot of patients suffer from them. However, if Koh’s research continues and neural stem cells can be conserved and recovered, those aftereffects could see improvement. Currently there are many projects in line with his study, funded by Korea's Ministry of Science, ICT and Future Planning and the Ministry of Health and Welfare. Koh is also participating in a joint study with Harvard University, which centers on the connection and networks between cells and neural cells in a pathologic condition, and whether that would lead to a recovery or not.

“When doing research, it is nice to get the results you desire, but this isn’t easy in most cases. I try to think positively though, because I believe that even bad results could turn out to be a trigger for another good research,” remarked Koh with a smile. The ultimate goal of Koh’s study is developing treatment for patients who are already diagnosed with brain-related diseases, by studying the proliferation and regeneration of neural stem cells. Koh added that he is also interested in researching how to enhance patients' memory and their cognitive functions. “It's regrettably sad how lot of research has been done, but there is no specific treatment for neural diseases. As a doctor responsible for curing patients, I want to try my best to help them by improving their conditions through my research, also contributing to the development of science as I go,” said Koh.

Koh continues to seek methods to enhance patients' conditions who are already diagnosed with cerebral infarction and Alzheimer's disease.